The purpose of these studies is to establish a better understanding of energy metabolism in tissues in vivo. Toward this goal, this laboratory concentrates on the use of non-invasive and non-destructive techniques to evaluate the biochemical and physiological function of. the heart with regard to energy utilization. These techniques include optical and nuclear magnetic resonance (NMR) spectroscopy to monitor various aspects of tissue function. In the past year we have concentrated on establishing the cytosolic feedback mechanism operating between oxidative phosphorylation and mechanical work in the intact heart. The follow major findings were made: 1) Using specific inhibitors, we have found that the putative ATP sensitive K-channel in the heart vasculature is active under resting conditions in vivo and plays an important role in the regulation of basal coronary vascular tone. This suggests that the regulation of cardiac blood flow by work may be orchestrated by the modulation of this metabolite sensitive channel. Furthermore, these studies indicate that the use of ATP sensitive K-channel blocking agents as oral drugs for diabetics may interfere with the normal regulation of coronary blood flow. 2) Studies using 13C labeled glucose in vivo have revealed that glycogen is not broken down during beta-agonist stimulation and glycogen synthesis is doubled after the stimulation. These data suggest that glycogen is not recruited as a metabolic substrate during myocardial work, but incoming glucose is redirected to oxidative pathways and not glycogen synthesis. 3) Studies on the effect of KC1 arrest on the heart revealed a change in the creatine kinase equilibrium. However, this was explained by a rise in intracellular pH with increasing extracellular K.